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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Granitzer, S; Widhalm, R; Ellinger, I; Zeisler, H; Forsthuber, M; Foessleitner, P; Geschrey, E; Saleh, L; Knöfler, M; Desoye, G; Ettel, P; Weichhart, T; Musiejovsky, L; Schabbauer, G; Salzer, H; Rosner, M; Hengstschläger, M; Gundacker, C.
LAT1-NRF2 axis controls sFlt-1/PlGF imbalance and oxidative stress in preeclampsia.
Nat Commun. 2025; 16(1):9112 Doi: 10.1038/s41467-025-64160-0 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz

Desoye Gernot

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Abstract:

Preeclampsia (PE) is a complex disease with unclear etiology. It is the most dangerous human pregnancy disease, causing morbidity and mortality in thousands of women and newborns worldwide. The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is currently the best and only predictive biomarker. The higher the ratio, the more likely the pregnant women will develop PE. The molecular mechanism underlying the increased sFlt-1/PlGF ratio is not known. Here, we show that amino acid transporter LAT1 (SLC7A5) and transcription factor NRF2 regulate this ratio via a previously unknown mechanism to produce sFlt-1 and PlGF in an anti-angiogenic ratio as observed in PE. In addition, we show that PE-associated oxidative stress, whose origin was unknown, is a secondary phenomenon caused by reduced NRF2 and LAT1 activity. The interdependence of the involved proteins, including also ATF4, Flt-1 and Akt, indicates that any disruption of the interaction would ultimately lead to a PE-like phenotype.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Female - administration & dosage

Vascular Endothelial Growth Factor Receptor-1 - metabolism, genetics, blood

NF-E2-Related Factor 2 - metabolism, genetics

Pre-Eclampsia - metabolism, genetics

Pregnancy - administration & dosage

Placenta Growth Factor - metabolism, blood, genetics

Oxidative Stress - administration & dosage

Large Neutral Amino Acid-Transporter 1 - metabolism, genetics

Signal Transduction - administration & dosage

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